title: Multimodal evaluation of in vivo magnetic resonance imaging of myocardial restoration by mouse embryonic stem cells.
abstract: OBJECTIVE
  Mouse embryonic stem cells have demonstrated potential to restore infarcted myocardium after acute myocardial infarction. Although the underlying mechanism remains controversial, magnetic resonance imaging has provided reliable in vivo assessment of functional recovery after cellular transplants. Multimodal comparison of the restorative effects of mouse embryonic stem cells and mouse embryonic fibroblasts was performed to validate magnetic resonance imaging data and provide mechanistic insight.
  
  
  METHODS
  SCID-beige mice (n = 55) underwent coronary artery ligation followed by injection of 2.5 x 10(5) mouse embryonic stem cells, 2.5 x 10(5) mouse embryonic fibroblasts, or normal saline solution. In vivo magnetic resonance imaging of myocardial restoration by mouse embryonic stem cells was evaluated by (1) in vivo pressure-volume loops, (2) in vivo bioluminescence imaging, and (3) ex vivo TaqMan (Roche Molecular Diagnostics, Pleasanton, Calif) polymerase chain reaction and immunohistologic examination.
  
  
  RESULTS
  In vivo magnetic resonance imaging demonstrated significant improvement in left ventricular ejection fraction at 1 week in the mouse embryonic stem cell group. This finding was validated with (1) pressure-volume loop analysis demonstrating significantly improved systolic and diastolic functions, (2) bioluminescence imaging and polymerase chain reaction showing superior posttransplant survival of mouse embryonic stem cells, (3) immunohistologic identification of cardiac phenotype within engrafted mouse embryonic stem cells, and (4) polymerase chain reaction measuring increased expressions of angiogenic and antiapoptotic genes and decreased expressions of antifibrotic genes.
  
  
  CONCLUSIONS
  This study validates in vivo magnetic resonance imaging as an effective means of evaluating the restorative potential of mouse embryonic stem cells.
authors.affiliation: Department of Cardiothoracic Surgery, Stanford University School of Medicine, Stanford University, Stanford, California 94305, USA.
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Hendry
authors.forename: Koen E A
authors.initials: KE
authors.lastname: van der Bogt
authors.forename: Ahmad Y
authors.initials: AY
authors.lastname: Sheikh
authors.forename: Takayasu
authors.initials: T
authors.lastname: Arai
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Dylla
authors.forename: Micha
authors.initials: M
authors.lastname: Drukker
authors.forename: Michael V
authors.initials: MV
authors.lastname: McConnell
authors.forename: Ingo
authors.initials: I
authors.lastname: Kutschka
authors.forename: Grant
authors.initials: G
authors.lastname: Hoyt
authors.forename: Feng
authors.initials: F
authors.lastname: Cao
authors.forename: Irving L
authors.initials: IL
authors.lastname: Weissman
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Connolly
authors.forename: Marc P
authors.initials: MP
authors.lastname: Pelletier
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Wu
authors.forename: Robert C
authors.initials: RC
authors.lastname: Robbins
authors.forename: Phillip C
authors.initials: PC
authors.lastname: Yang
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D053595:Embryonic Stem Cells / Q000473:pathology / Q000637:transplantation*; D005260:Female; D005347:Fibroblasts / Q000637:transplantation; D006084:Graft Rejection; D006085:Graft Survival; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D016513:Mice, SCID; D009200:Myocardial Contraction / Q000502:physiology; D009203:Myocardial Infarction / Q000473:pathology* / Q000601:surgery*; D032383:Myocytes, Cardiac / Q000473:pathology; D011897:Random Allocation; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D033581:Stem Cell Transplantation / Q000379:methods*; D013318:Stroke Volume; D020257:Ventricular Remodeling / Q000502:physiology*